In the MASTER trial, researchers hypothesized that
≥75% of patients with newly diagnosed MM who received
quadruplet therapy with Dara-KRd, autologous hemato-
poietic cell transplantation (AHCT), and MRD-based,
response-adapted consolidation therapy with Dara-KRd
would reach MRD-negative status. The primary endpoint
of the study was MRD-negative remission (<10 -5 ) as defined
by International Myeloma Working Group (IMWG) criteria.
MRD testing of bone marrow samples was performed
after induction, AHCT, and consolidation. Per study proto-
col, patients received therapy until they had two consecutive
MRD-negative (<10 -5 ) readings, either post-induction and
post-transplant, or post-transplant and during consolida-
tion. Patients who reached MRD negativity did not receive
further therapy and instead were observed with MRD
surveillance at 6 and 18 months after treatment discontin-
uation. Patients who completed consolidation therapy and
remained MRD-positive received lenalidomide maintenance.
Eligible patients had newly diagnosed MM with measur-
able disease, were previously untreated except for up to 1
cycle of bortezomib, cyclophosphamide, and dexamethasone
(VCD), had creatinine levels >40 mL, adequate liver and car-
diac function, and an ECOG performance status of ≤2.
The 4 induction cycles consisted of:
• daratumumab 16 mg/kg IV on days 1, 8, 15, and 22
• carfilzomib 56 mg/m 2 IV on days 1, 8, and 15
• lenalidomide 25 mg orally on days 1-21
standard-risk and high-risk cytogenetic abnormalities, Dr.
Costa noted.
At the time of the presentation, 26 patients (19 with
standard-risk cytogenetics and 7 with high-risk cytoge-
netics) had confirmed MRD negativity and entered treat-
ment-free observation. After a median follow-up of 4.9
months (range = 0.2-12.2), there was no relapse or resur-
gence of MRD among this group.
Dr. Costa reported that all patients had at least a partial
response (PR) by the end of the second induction cycle.
After induction, 92% of patients obtained a very good PR or
better, including 39% who experienced a stringent complete
response.
Based on these results, “Intense quadruplet therapy and
achievement of confirmed MRD-negative complete response
may enable safe transition to observation or MRD surveil-
lance and reduce the physical and financial burden of con-
tinuous therapy,” Dr. Costa said. However, these results are
limited by the non-randomized design, the small number of
enrolled patients, and the short duration of follow-up. The
MASTER trial is still accruing patients, and it is expected to
reach 123 patients to better inform outcomes.
The authors report relationships with Amgen and Janssen,
which supported this trial.
Reference
Costa L, Chhabra S, Godby K, et al. Daratumumab, carfilzomib, lenalidomide and dexamethasone
(Dara-KRd) induction, autologous transplantation and post-transplant, response-adapted,
measurable residual disease (MRD)-based Dara-Krd consolidation in patients with newly diagnosed
multiple myeloma (NDMM). Abstract #653. Presented at the 2019 American Society of Hematology
Annual Meeting, December 7, 2019; Orlando, FL.
• dexamethasone 40 mg orally/IV on days 1, 8, 15, 22
(repeated every 28 days)
Induction was followed by AHCT and response-adapted con-
solidation, consisting of either 0, 4, or 8 cycles of Dara-KRd
consolidation therapy, depending on depth of MRD.
Dr. Costa presented results from 81 enrolled patients
who received at least 2 cycles of induction therapy. Although
there was no age limit, the median age was 61 years (range
= 36-78). Nearly one-third of patients (29%; n=20) had high-
risk chromosomal abnormalities, including del17p, t(4;14),
or t(14;16).
After a median follow-up of 7.4 months (range = 2.1-20),
no patients discontinued treatment due to toxicity. Howev-
er, 2 deaths were reported: 1 from metapneumovirus 9 days
after AHCT and 1 sudden death 58 days after AHCT. Serious
adverse events included pneumonia (n=5), fever and neutro-
penia (n=2), pulmonary embolism (n=1), atypical hemolytic
uremic syndrome (n=1), infusion-related reactions (n=1),
and atrial fibrillation (n=1).
MRD was evaluable in 96% of patients (n=78). Overall,
40% of patients achieved the primary endpoint after the
induction period, 73% after transplant, and 82% after con-
solidation. These rates were similar between patients with
Can Patients With Limited-
Stage Diffuse Large B-Cell
Lymphoma Skip Radiation
Therapy?
Results from the Intergroup National Clinical Trials Network (NCTN)
study S1001 demonstrated that 89% of patients with limited-stage
diffuse large B-cell lymphoma (DLBCL) maintained survival outcomes
at 5 years, after PET-directed therapy with 4 cycles of R-CHOP
(rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). 1
These findings, presented at the 2019 ASH Annual Meeting, suggest
that most patients can avoid receiving radiation therapy.
“Diffuse large B-cell lymphoma presents as limited-
stage in about 30% of [patients],” said lead investi-
gator Daniel O. Persky, MD, from the University of
Arizona Cancer Center in Tucson. While patients with
March 2020
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